Efficacy and safety of sirolimus in lymphangioleiomyomatosis (MILES)

McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, …, Trapnell BC · 2011 · New England Journal of Medicine · Atlas ID MCC2011

What this study shows

MILES was a 12-month placebo-controlled trial of sirolimus in 89 women with lymphangioleiomyomatosis (LAM), a rare lung disease driven by overactive mTOR. On placebo, lung function (FEV1) fell by about 12 ml a month. On sirolimus it held steady (+1 ml a month), a 153 ml difference over the year. In the next year nobody took the drug, and the sirolimus group's decline resumed in parallel with placebo, so the benefit lasted only while the drug was taken. Walking distance and gas-transfer capacity did not improve. Boundary: patients had fairly advanced disease (average FEV1 about 48% of predicted), many dropped out of the observation year, and mouth ulcers and rashes may have revealed who was on the drug. Sirolimus was held at a blood level of 5 to 15 ng/ml, so this was continuous dosing, not intermittent.

Abstract

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Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease in women; it is associated with inappropriate activation of mammalian target of rapamycin (mTOR) signaling, which regulates cellular growth and lymphangiogenesis. Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1-2 trials involving patients with LAM. We conducted a two-stage trial of sirolimus involving 89 patients with LAM who had moderate lung impairment--a 12-month randomized, double-blind comparison of sirolimus with placebo, followed by a 12-month observation period.

Read the full abstract on PubMed →

At a glance

Evidence type	H Human study Marked H because it is direct evidence from a human clinical trial or human cohort; the code names the kind of study, not its quality -- a small, well-run trial is still H.
Study type	2 - Human Clinical Trial
Model system	Humans, RCT (n=89, women with LAM)
Journal	New England Journal of Medicine
Year	2011
Peer reviewed	Yes
Record last updated	2026-07-29
Source	DOI 10.1056/NEJMoa1100391 · PMID 21410393 · Free full text (PMC3118601)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Sirolimus (rapamycin)
Target	mTOR
Model	Human – RCT (MILES, n=89, women with LAM)
Effect	Sirolimus stabilized lung function (FEV1) in lymphangioleiomyomatosis during treatment
Dose	Oral sirolimus, initial 2 mg/day titrated to trough 5-15 ng/ml; 12-month double-blind treatment + 12-month observation off-drug; 1:1 vs placebo (MILES).
Sample size	111 consented, 89 randomized (43 placebo / 46 sirolimus); women with LAM, FEV1 <=70% predicted.
Effect size	Primary outcome FEV1 slope (mL/month): sirolimus stabilized lung function during treatment while placebo declined; benefit waned after stopping the drug.
Limitations	Interim analysis delayed by site/contracting issues; other health-symptom measures not significantly different; benefit tied to continued dosing.

In the Atlas

Links in the pathway map

Supports Rapamycin inhibits Lymphangioleiomyomatosis

Answers that reference this study

Discussed in the plain-language answer Are sirolimus and everolimus the same drug?.

Cite this paper

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McCormack, F. X., Inoue, Y., Moss, J., Singer, L. G., Strange, C., Nakata, K., Barker, A. F., Chapman, J. T., Brantly, M. L., Stocks, J. M., Brown, K. K., Lynch, J. P., Goldberg, H. J., Young, L. R., Kinder, B. W., Downey, G. P., Sullivan, E. J., Colby, T. V., McKay, R. T., Cohen, M. M., Korbee, L., Taveira-DaSilva, A. M., Lee, H. S., Krischer, J. P., & Trapnell, B. C. (2011). Efficacy and safety of sirolimus in lymphangioleiomyomatosis (MILES). New England Journal of Medicine. https://doi.org/10.1056/NEJMoa1100391

@article{MCC2011,
  author       = {McCormack, F. X. and Inoue, Y. and Moss, J. and Singer, L. G. and Strange, C. and Nakata, K. and Barker, A. F. and Chapman, J. T. and Brantly, M. L. and Stocks, J. M. and Brown, K. K. and Lynch, J. P. and Goldberg, H. J. and Young, L. R. and Kinder, B. W. and Downey, G. P. and Sullivan, E. J. and Colby, T. V. and McKay, R. T. and Cohen, M. M. and Korbee, L. and Taveira-DaSilva, A. M. and Lee, H. S. and Krischer, J. P. and Trapnell, B. C.},
  title        = {{Efficacy and safety of sirolimus in lymphangioleiomyomatosis (MILES)}},
  journal      = {New England Journal of Medicine},
  year         = {2011},
  doi          = {10.1056/NEJMoa1100391},
  note         = {PMID: 21410393},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record MCC2011) [Data set]. https://mtor-atlas.org/study/MCC2011/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_MCC2011,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record MCC2011},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/MCC2011/},
  doi          = {10.5281/zenodo.22059963}
}

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